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COMMON INFECTIONS IN PRIMARY CARE
Brandon Dionne, PharmD, BCPS-AQ ID, BCIDP, AAHIVP
Assistant Clinical Professor
Northeastern University School of Pharmacy
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OBJECTIVES
¡ Identify the most common pathogens causing urinary tract infections (UTIs), skin and soft tissue infections (SSTIs), and respiratory tract infections (RTIs)
¡ Develop an appropriate empiric treatment plan for a patient’s infection based on risk factors
¡ Modify an empiric regimen or start a definitive therapy based on culture data and/or patient progress
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INTERPRETING SUSCEPTIBILITIES
¡ Susceptibility results often include minimum inhibitory concentrations (MICs)
¡ MICs cannot be compared between antibiotics
¡ Use the interpretations (S, I, or R) to guide therapy
¡ S is susceptible/sensitive – safe to use
¡ I is intermediate – may be OK if higher dose can be used or drug concentrates at site of infection
¡ R is resistant – antibiotic should not be used
¡ Breakpoints are set by the Clinical Laboratory Standards Institute (CLSI) in the M100
¡ Freely available online - https://clsi.org/standards/products/free-resources/access-our-free-resources/
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URINARY TRACT INFECTIONS
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EPIDEMIOLOGY
¡ UTIs are one of the most common bacterial infections, affecting 150 million people each year worldwide
¡ 10.5 million office visits and 2–3 million emergency department visits in the United States in 2007
¡ Female >> male
¡ ~50% of women will suffer ≥ 1 episode of UTI in their lifetime
¡ Prevalence increases with age
¡ Age > 65: female ≈ male
Flores-Mireles AL, et al. Nat Rev Microbiol. 2015;13(5):269–284.Walsh C, et al. Surgery (Oxford). 2017: 35:6; 293-298.
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ETIOLOGY
Flores-Mireles AL, et al. Nat Rev Microbiol. 2015;13(5):269–284.
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UTI CLASSIFICATIONS
Uncomplicated UTI
¡ No structural or functional abnormality of the urinary tract
¡ Healthy, non-pregnant, pre-menopausal adult women
Complicated UTI¡ Structural or functional abnormality of urinary tract
¡ Neurogenic bladder ¡ Kidney stones ¡ Catheter or stent or instrumentation
¡ Underlying conditions ¡ Pregnancy¡ Men; children; elderly¡ Immunocompromised¡ Hospital acquired infection
Flores-Mireles AL, et al. Nat Rev Microbiol. 2015;13(5):269–284.Walsh C, et al. Surgery (Oxford). 2017: 35:6; 293-298.
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URINE DIPSTICK
¡ Reagent strip testing of urine sample
¡ Advantages: rapid, inexpensive, and easy to use
¡ Disadvantages: less sensitive and specific than urine culture
¡ Used to detect leukocyte esterase and nitrites
https://www.alibaba.com/product-detail/rapid-response-urine-dipstick-10-parameter_60062233181.html
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URINALYSIS
¡ Bacteria
¡ Usually semi-quantitative
¡ Nitrite
¡ (+) bacteria that reduce nitrate¡ Enteric gram negative rods (i.e., Enterobacterales)
¡ (-) bacteria that do not reduce nitrate
¡ S. saprophyticus
¡ Enterococcus spp.
¡ Pseudomonas aeruginosa
¡ Pyuria
¡ WBC >10 cells/hpf
¡ Leukocyte esterase – semi quantitative
¡ WBC casts
¡ Indicative of pyelonephritis
¡ Squamous epithelial cells
¡ >5-10 cells/hpf suggests contamination
¡ Hematuria
¡ Proteinuria
Simerville, et al. Am Fam Physician. 2005;71(6):1153-1162.
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URINALYSIS SUMMARY
Characteristic (-) UTI (+) UTI Appearance Clear Cloudy/hazy
Bacteria (-) (+)Nitrite (-) (+/-)
Leukocyte esterase (-) < small < moderate < large WBC 0-5 cells/mm3 >5-10 cells/mm3
WBC casts (-) (+/-)
Squamous epithelial cells None or few = good sampleMany = contamination (recollect)
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URINE CULTURE
¡ Urine culture generally NOT necessary for acute uncomplicated cystitis
¡ Pathogens usually predictable
¡ Therapy may be completed before culture results are known
¡ When to culture:
¡ Recurrent UTI
¡ Pyelonephritis
¡ Male
¡ Pregnancy
¡ Typically 103 cfu/mL for catheterized and 105 cfu/mL for clean catch considered significant bacteriuria
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ASYMPTOMATIC BACTERIURIA
¡ Bacteriuria without genitourinary signs or symptoms
¡ Common in healthy young women
¡ Common in elderly (> 65 years)
¡ Treatment of asymptomatic bacteriuria increases risk of UTI with MDROs
¡ Should only be treated in select populations:
¡ Pregnant women – 4-7 days
¡ Patients undergoing a urologic procedure with anticipated mucosal trauma – 1-2 doses
¡ Kidney transplant in past month??
¡ Neutropenia??
Nicolle LE, et al. Clin Infect Dis. 2019;68(10):1611-1615.Cai T, et al. Clin Infect Dis. 2012;55(6):771.
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UTI TREATMENT
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GOALS OF THERAPY
¡ Eradicate invading organism(s)
¡ Treat or prevent systemic manifestations
¡ Prevent recurrence
¡ Minimize potential for collateral damage
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COLLATERAL DAMAGE
¡ Ecological adverse effects of antimicrobial therapy
¡ Leads to the selection of drug resistant organisms & colonization/infection with multidrug resistant organisms
¡ Associated with broad spectrum cephalosporins and fluoroquinolones
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PK OF UTI ANTIBIOTICS
Antibiotic Oral Dose (mg) Peak Cserum (mg/L ) Peak Curine (mg/L )Amoxicillin 250
5003.5-5.05.5-11.0
305-865772
Cephalexin 250500
915-18
830110
TMP/SMX 160/800 1-2/40-60 74/190
Ciprofloxacin 250500
0.8-1.91.6-2.9
>200350
Levofloxacin 500 5.7 521-771
Nitrofurantoin 100 <2 50-150
Fosfomycin 3000 26 1053-4415Gupta K, et al. Ann Intern Med. 2001;135(1):41-50.
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CYSTITIS
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UNCOMPLICATED CYSTITIS
¡ Most common type of UTI in non-pregnant, pre-menopausal women with no systemic disease ¡ Diagnosed based on urinary symptoms and urinalysis
¡ Urine culture is not necessary¡ Most likely organism is E. coli
¡ Short-course therapy preferred ¡ Improved adherence
¡ Fewer adverse effects ¡ Lower cost ¡ Less “collateral damage”
¡ Duration of therapy is dependent on antimicrobial agent
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Antibiotic (oral) Duration NotesNitrofurantoin monohydrate/ macrocyrstals 100mg po BID
5 days Drug of choice (DOC)Minimal resistance and low risk of collateral damage – avoid when CrCl <30 mL/minADRs: GI, peripheral neuropathy, pulmonary fibrosis
TMP/SMX 160/800mg (DS) po BID 3 days Avoid if local E. coli resistance rates >20%ADRs: Hyperkalemia, rash, thrombocytopenia
Fosfomycin 3g po x1 Single dose Minimal resistance and low risk of collateral damageActivity against ESBL- and KPC-producers vancomycin resistant Enterococcus spp. (VRE)ADRs: diarrhea, headache
Fluoroquinolones -Ciprofloxacin 250 mg po BID-Levofloxacin 250 mg or 500 mg po QD
3 days Rising prevalence of FQ resistanceReserved for patients without other antibiotic options due to severe disabling side effectsADRs: QTc prolongation, risk for C. difficile diarrhea
β-Lactam agents- Amoxicillin-clavulanate 500 mg/125 mg PO TID- Cefpodoxime 100 mg PO BID- Cefdinir 300 mg PO BID x3-7d
3-7 days Inferior efficacy High in vitro resistance rate ADRs: GI effects
Gupta K, et al. Clin Infect Dis. 2011; 52(5): e103-20.
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COMPLICATED CYSTITIS
¡ Infection of the lower urinary tract, plus presence of one of the following:¡ Pregnancy¡ Urinary catheter
¡ Male¡ Anatomic abnormality ¡ Functional abnormality
¡ Urinalysis and urine culture should be obtained ¡ Pathogens are not easily predicted ¡ Increased risk of resistance
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CYSTITIS IN PREGNANCY
¡ Increased risk of UTI during pregnancy
¡ Bacteriuria can progress to pyelonephritis
¡ Premature delivery or low birth weight infants
¡ Guidelines recommend screening pregnant women for bacteriuria by urine culture at least once in early pregnancy and intermittently throughout
¡ Pregnant women should be treated for both asymptomatic and symptomatic bacteriuria
¡ Follow up culture after treatment completion
Nicolle LE, et al. Clin Infect Dis. 2005; 40(5): 643-54.Matuszkiewicz-Rowińska J, et al. Arch Med Sci. 2015;11(1):67-77.
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ANTIBIOTIC OPTIONS IN PREGNANCY
Antibiotic (oral) Duration of Treatment
Notes
β-Lactam agents- Amox/clav 500 mg/125 mg PO TID- Cephalexin 500 mg po BID- Cefpodoxime 100 mg PO BID- Cefuroxime 250 mg PO BID
5-7 days Pregnancy category B
Nitrofurantoin monohydrate 100mg po BID 5-7 days Pregnancy category B (avoid after 38th week of gestation due to risk of hemolytic anemia)
TMP/SMX 160/800mg (DS) po BID 5-7 days Pregnancy category D (avoid in 1st trimester due to risk for neural tube defects and after 38th
week due to risk of kernicterus)
Matuszkiewicz-Rowińska J, et al. Arch Med Sci. 2015;11(1):67-77.
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ANTIBIOTICS TO AVOID IN PREGNANCY
AVOID:
¡ Fluoroquinolones
¡ Pregnancy category C
¡ Fetal cartilage development disorders
¡ Tetracyclines
¡ Pregnancy category D
¡ Embryotoxicity and retardation of skeletal development
Matuszkiewicz-Rowińska J, et al. Arch Med Sci. 2015;11(1):67-77.
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OUTPATIENT PYELONEPHRITIS TREATMENT
Antibiotic (oral) Duration NotesFluoroquinolones -Ciprofloxacin 500 mg po BID-Levofloxacin 750 mg po QD (+/-)IV FQ+ or IV ceftriaxone or IV aminoglycoside$
7 days 5 days
1 dose 1 dose
+ If local FQ resistance is <10%$ If local FQ resistance is > 10%
TMP/SMX 160/800mg (DS) po BID (+/-)IV ceftriaxone or IV aminoglycoside#
14 days 1 dose
If causative bacteria is susceptible #TMP/SMX susceptibility is unknownHigh-dose extended-interval dosing of aminoglycoside
β-Lactam agents (po)*
IV ceftriaxone or IV aminoglycoside10-14 days 1 dose
*Inferior efficacy and need combinationwith parenteral antibiotic therapy
Gupta K, et al. Clin Infect Dis. 2011; 52(5): e103-20.
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RECURRENT UTIs: ≥ 2 WITHIN 6 MONTHS OR ≥ 3 WITHIN 1 YEAR
Relapse/Persistence: occurs ≤ 2 weeks of UTI,
§ Involves the same organism
§ Usually due to:
§ Functional abnormalities
§ Structural abnormalities
§ Chronic bacterial prostatitis
Reinfection: occurs > 2 weeks after last UTI
¡ Typically involves a different organism
¡ More common than relapse
¡ May be due to:
¡ Sexual intercourse
¡ Diaphragm/spermicide use
Dason S, et al. Can Urol Assoc J. 2011; 5(5):316-322.
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TREATMENT OF RELAPSE UTI
¡ Repeat culture and susceptibility testing
¡ Imaging and specialist referral
¡ Remove obstruction if any
¡ Rule out chronic bacterial prostatitis in male
¡ Prolonged treatment duration
Dason S, et al. Can Urol Assoc J. 2011; 5(5):316-322.
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PROPHYLAXIS OF REINFECTION UTI
Associated with sexual activity à Post-coital prophylaxis
¡ TMP/SMX 80/400 mg (SS tab) PO x1
¡ Nitrofurantoin 50-100 mg PO x1
¡ Cephalexin 250 mg PO x1
¡ Ciprofloxacin 125 mg PO x1
Unknown etiology with symptoms àLong-term prophylaxis ~6 mo
¡ TMP/SMX SS ½ tab (40/200 mg) PO QD or TIW
¡ Nitrofurantoin 50 mg or 100 mg PO QD
¡ Cephalexin 125 mg or 250 mg PO QD
¡ Fosfomycin 3 g q10days
¡ If infection occurs, switch to conventional treatment regimen, then resume prophylaxis
Albert X, et al. Cochrane Database Syst Rev. 2004;(3):CD001209.
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SELF-CARE
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URINARY ANALGESICS
¡ Phenazopyridine [Pyridium (RX); AZO (OTC)] 200 mg TID
¡ Indication: Provides symptomatic relief of dysuria, urgency and frequency for MAX of 2 days
¡ Common ADRs: red/orange discoloration of body fluids, headache, GI
¡ Serious ADRs: rash, anaphylaxis, hemolytic anemia
¡ Disadvantages:
¡ May mask symptoms of untreated UTI
¡ Contraindicated if CrCl <50 mL/min, hepatic insufficiency
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PREVENTATIVE STRATEGIES
¡ Fluids/hydration – 2-3 L/day
¡ Dilute urine/bacterial inoculum
¡ Promote increased voiding
¡ Cranberry juice, capsules, or tablets
¡ Thought to disrupt bacterial adherence to bladder epithelial cells
¡ Design flaws and heterogeneity in data and products
¡ Many show no benefit
¡ Limit use of spermicides
¡ Lactobacillus probiotics
¡ Normalize vaginal pH, regulating genitourinary flora
¡ Topical estrogen replacement for postmenopausal women with recurrent UTI
¡ Promote lactobacilli growth in vaginal flora
¡ Methenamine (Cystex, AZO UT Defense)
¡ D-mannose – not much data
Hooton TM, et al. JAMA Intern Med. 2018;178(11):1509-1515.
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SKIN AND SOFT TISSUE INFECTIONS
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EPIDEMIOLOGY
¡ Cause 48.5 infections per 1,000 patient-years
¡ Staphylococcus aureus SSTIs doubled from 57 to 117 cases per 100,000 patient-years between 2001-2009
¡ From 2005-2009, community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) infections increased by 34%
Kaye KS, et al. Clin Infect Dis. 2019;68(suppl 3): S193–S199.
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SSTI CLASSIFICATIONS
Non-Purulent SSTI
¡ Impetigo
¡ Erysipelas
¡ Cellulitis
Purulent SSTI
¡ Furuncle
¡ Carbuncle
¡ Abscess
Stevens DL, et al. Clin Infect Dis. 2014;59(2):E10-E52.
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ETIOLOGY
Non-purulent
¡ Beta-hemolytic Streptococcus spp. (especially Streptococcus pyogenes) are the most common causes of cellulitis
¡ Staphyloccus aureus can cause impetigo
¡ Capnocytophaga canimorsus and Pasteurella multocida can be involved in dog and cat bites
Purulent
¡ Staphylococcus aureus is the most common cause
¡ Risk factors for methicillin-resistance (MRSA)
¡ Nasal colonization
¡ Prior MRSA infection
¡ Recent hospitalization
¡ Recent antibiotics
Kaye KS, et al. Clin Infect Dis. 2019;68(suppl 3): S193–S199.
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NON-PURULENT CELLULITIS TREATMENT
¡ Mild – no evidence of systemic symptoms
¡ Penicillin 500 mg PO q6h
¡ Dicloxacillin 500 mg PO q6h
¡ Cephalexin 500 mg PO q6h (or cefadroxil 1 g PO q12-24h)
¡ Clindamycin 300 mg PO q6-8h if severe beta-lactam allergy
¡ Moderate – one sign of systemic symptoms
¡ Requires intravenous antibiotics
Stevens DL, et al. Clin Infect Dis. 2014;59(2):E10-E52.
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PURULENT SSTI TREATMENT
¡ Incision and drainage is the most important step – send for culture and susceptibility
¡ Mild – area of purulence <5 cm
¡ Guidelines recommend against antibiotics
¡ Clinical trials of antibiotics improve cure by about 10% vs I+D alone (70% vs 80%)
¡ Moderate – area of purulence >5 cm, failure of I+D alone, or one sign of systemic infection
¡ Trimethoprim/sulfamethoxazole 1 or 2 DS PO q12h for at least 5 days
¡ Doxycycline 100 mg PO q12h for at least 5 days
Stevens DL, et al. Clin Infect Dis. 2014;59(2):E10-E52.
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ANIMAL BITE TREATMENT
¡ Irrigation of wound
¡ Target gram-positive and anaerobic bacteria
¡ Amoxicillin/clavulanate 875/125 mg PO q12h
¡ Give tetanus vaccine if >10 years since last vaccination
¡ Generally should not be closed unless near face
Stevens DL, et al. Clin Infect Dis. 2014;59(2):E10-E52.
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RESPIRATORY TRACT INFECTIONS
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CLASSIFICATIONS
Upper Respiratory Tract Infections
¡ Acute otitis media
¡ Rhinosinusitis
¡ Pharyngitis
Lower Respiratory Tract Infections
¡ Bronchitis
¡ Community-acquired pneumonia
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ACUTE OTITIS MEDIA
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EPIDEMIOLOGY
¡ 11th most common reason for an emergency department visit
¡ 15th most common reason for an office visit
¡ 75% of children <1 yo will have ≥1 episode
¡ Costs almost $3 billion annually in the US
Hing E, et al. Adv Data. 2006(374):1-33.McCaig LF, Nawar EW. Adv Data. 2006(372):1-29.Faden H, et al. Pediatr Infect Dis J. 1998;17(12):1105-12.Soni A. Agency for Healthcare Research and Quality, 2008.
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ETIOLOGY
¡ 40-75% of cases are caused by viruses
¡ Most common bacterial pathogens
¡ Streptococcus pneumoniae (35-40%)
¡ Haemophilus influenzae (30-35%)
¡ Moraxella catarrhalis (15-18%)
AAP Subcommittee on Management of AOM. Pediatrics. 2004; 113(5):1451–1465.Wald ER. Clin Infect Dis. 2011;52(Suppl 4):S277–S283.
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SEVERITY OF AOM
¡ Severe
¡ Moderate or severe otalgia for ≥48 h
-OR-
¡ Temperature ≥39°C
¡ Non-severe¡ Mild otalgia for <48 h
-AND-
¡ Temperature <39°C
¡ Bilateral vs. Unilateral
Lieberthal AS, et al. Pediatrics. 2013;131(3):e964-99.
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TREATMENT DURATION
Age Otorrhea Severe Non-severe bilateral
Non-severe unilateral
<6 months 10 days ABX 10 days ABX 10 days ABX 10 days ABX
6-23 months 10 days ABX 10 days ABX 10 days ABX Observe or 10 days ABX
2-5 years 10 days ABX 10 days ABX Observe or 7 days ABX
Observe or 7 days ABX
≥6 years 10 days ABX 10 days ABX Observe or 5-7 days ABX
Observe or 5-7 days ABX
• Observe for 48-72 h with follow-up and access to clinician/antibiotics if the symptoms do not improve within 2-3 days or worsen at any time
Lieberthal AS, et al. Pediatrics. 2013;131(3):e964-99.
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TREATMENT
Initial immediate or delayed therapy Antibiotic treatment after failure
First-line therapy Alternative (PCN allergy) First-line therapy Alternative
Amoxicillin 80-90mg/kg/day PO bid
OR
Amoxicillin/clavulanate 90mg/kg/day of amoxicillin and 6.4 mg/kg/day of clavulanate PO bid
Cefdinir 14 mg/kg/day POonce daily-bid
Cefuroxime 30 mg/kg/day PO bid
Cefpodoxime 10 mg/kg/day PO bid
Ceftriaxone 50 mg/kg/dayIM or IV for 1 to 3 days
Amoxicillin/clavulanate 90mg/kg/day of amoxicillin and 6.4 mg/kg/day of clavulanate PO bid
OR
Ceftriaxone 50 mg/kg/dayIM or IV for 3 days
Clindamycin 30-40 mg/kg/day PO tid with or without a 3rd generation cephalosporin
Failure of second ABXClindamycin 30-40 mg/kg/day PO tid plus a 3rd
generation cephalosporin
Tympanocentesis
Consult specialistLieberthal AS, et al. Pediatrics. 2013;131(3):e964-99.
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TREATMENT FAILURE
¡ Clinical improvement should be noted within 48-72 hours¡ Resolution of fever¡ Improvement in irritability or fussiness
¡ Symptoms may initially worsen after diagnosis of AOM¡ Should begin to improve 24 hours after diagnosis
¡ If symptoms do not improve, can consider switching antibiotics¡ Amoxicillin à amox/clav¡ Amox/clav à ceftriaxone
¡ Consider tympanocentesis if still no improvement¡ Gram stain, culture, and susceptibilities
Lieberthal AS, et al. Pediatrics. 2013;131(3):e964-99.
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PREVENTION
¡ Immunizations
¡ Prevnar 13
¡ Hib
¡ Annual influenza
¡ Breastfeeding
¡ At least 6 months
¡ Avoid tobacco smoke
Lieberthal AS, et al. Pediatrics. 2013;131(3):e964-99.
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RHINOSINUSITIS
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EPIDEMIOLOGY
¡ ~30 million cases are diagnosed annually in the US
¡ ~1 in 5 antibiotics prescribed in the US is for sinusitis
¡ Adults with sinusitis miss ~6 workdays/year
¡ Patients with sinusitis are more likely to
¡ Use the emergency room
¡ Spend more than $500/year on care
¡ See a medical specialist
Schiller JS, et al. Vital Health Stat. 10 2012;(252):1–207.Gill JM, et al. Fam Med. 2006;38(5):349–354.Bhattacharyya N.. Am J Rhinol Allergy. 2009;23(4): 392–395.
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ETIOLOGY
¡ Viruses are responsible for most cases of acute sinusitis
¡ ~90-98% of cases
¡ Antibiotics prescribed for 81% of adults with sinusitis
¡ In RCTs, ~70% of patients improve spontaneously
¡ Acute bacterial rhinosinusitis (ABRS) causes
¡ Streptococcus pneumoniae
¡ Haemophilus influenzae
¡ Moraxella catarrhalis
Gwaltney JM Jr, et al.. Clin Infect Dis. 2004;38:227–33.Young J, et al. Lancet. 2008;371:908–14.Chow AW, et al. Clin Infect Dis. 2012;54(8):e72-112.
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WHEN TO TREAT WITH ANTIBIOTICS
¡ Persistent signs and symptoms¡ ≥10 days without any evidence of improvement
¡ Severe signs and symptoms¡ High fever ≥39°C-AND-¡ Purulent nasal discharge or facial pain≥3-4 consecutive days at beginning of illness
¡ Worsening (or “double-sickening”) signs or symptoms ¡ New onset of fever, headache, or increase in nasal drainage¡ After 5-6 days of typical viral URI with improving symptoms
Chow AW, et al. Clin Infect Dis. 2012;54(8):e72-112.
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COLDS
https://xkcd.com/1612/
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TREATMENT OF CHILDREN (10-14 DAYS)
Indication First Line Second Line
Initial empiric therapy Amoxicillin/clavulanate45 mg/kg/day PO bid
Amoxicillin/clavulanate 90 mg/kg/day PO bid
β-lactam allergy
Type I hypersensitivity Levofloxacin 10-20 mg/kg/day PO q 12-24 h
Non-type I hypersensitivity
Clindamycin 30-40 mg/kg/day PO tid PLUS cefixime (8 mg/kg/day PO bid) or cefpodoxime (10 mg/kg/day PO bid)
Severe infection requiring hospitalization
Ampicillin/sulbactam 200-400 mg/kg/day IV q6h
Ceftriaxone 50 mg/kg/day IV q12h
Cefotaxime 100-200 mg/kg/day IV q6h
Levofloxacin 10-20 mg/kg/day IV q 12-24 h
Chow AW, et al. Clin Infect Dis. 2012;54(8):e72-112.
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TREATMENT OF ADULTS (5-7 DAYS)
Indication First Line Second Line
Initial empiric therapy Amoxicillin/clavulanate 500/125 mg PO tid or 875/125 mg PO bid
Amoxicillin/clavulanate 2000/125 mg PO bid
Doxycycline 100 mg PO bidβ-lactam allergy Doxycycline 100 mg PO bid
Levofloxacin 500 mg PO daily
Moxifloxacin 400 mg PO daily
Severe infection requiring hospitalization
Ampicillin/sulbactam 1.5-3 g IV q6h
Levofloxacin 500 mg PO or IV daily
Moxifloxacin 400 mg PO or IV daily
Ceftriaxone 1-2 g IV q 12-24 h
Cefotaxime 2 g IV q 4-6 hChow AW, et al. Clin Infect Dis. 2012;54(8):e72-112.
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WHEN TO USE HIGH-DOSE AMOXICILLIN/CLAVULANATE
¡ High endemic rates (≥10%) of penicillin non-susceptible S. pneumoniae¡ Severe infection
¡ Evidence of systemic toxicity¡ Fever ≥39°C¡ Threat of suppurative complications
¡ Attendance at daycare¡ Age <2 or >65 years¡ Recent hospitalization within past 5 days¡ Antibiotic use within past month¡ Immunocompromised or comorbid conditions
Chow AW, et al. Clin Infect Dis. 2012;54(8):e72-112.
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PHARYNGITIS
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EPIDEMIOLOGY
¡ Cause of ~2 million ED and office visits annually
¡ Costs about $1.2 billion annually
¡ Children 5-15 yo are the most affected age group
¡ Highest incidence in winter and early spring
Hing E, et al. Natl Health Stat Report. 2010; (28):1–32.Salkind AR, Wright JM. Value Health. 2008;11(4):621–627.Shulman ST, et al. Clin Infect Dis. 2012;55(10):e86-102.
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ETIOLOGY
¡ Viruses cause the majority of cases
¡ Rhinovirus (20%)
¡ Coronavirus (5%)
¡ Adenovirus (5%)
¡ HSV (4%)
¡ Group A β-hemolytic streptococci (GABHS, a.k.a. GAS or S. pyogenes)
¡ Causes 5-15% of cases in adults and 20-30% in children
Wessels MR. N Engl J Med. 2011;364(7):648–655.Shulman ST, et al. Clin Infect Dis. 2012;55(10):e86-102.
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PRESENTATION
Viral
¡ Conjunctivitis
¡ Coryza¡ Rhinorrhea
¡ Cough
¡ Oral Ulcers
¡ Hoarseness
¡ Diarrhea
¡ Rash
Bacterial
¡ Abrupt onset of sore throat
¡ Fever
¡ Headache
¡ GI upset
¡ Patchy exudates
¡ Palatal petichiae
¡ Scarlatiniform rash
¡ Anterior cervical adenitis
¡ Exposure to GAS pharyngitisShulman ST, et al. Clin Infect Dis. 2012;55(10):e86-102.
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TREATMENT
Drug Dose Duration
No penicillin allergy
Penicillin V Children: 250 mg PO bid-tidAdolescents and adults: 250 mg qid or 500 mg bid
10 days
Amoxicillin Children: 50 mg/kg/day PO once daily-bid (max = 1000 mg/day) 10 days
Benzathine penicillin <27 kg: 600,000 units IM once; ≥27 kg: 1,200,000 units IM once 1 dose
Penicillin allergy
Cephalexin 20 mg/kg/dose PO bid (max = 500 mg/dose) 10 days
Cefadroxil 30 mg/kg once PO once daily (max = 1000 mg) 10 days
Clindamycin 7 mg/kg/dose PO tid (max = 300 mg/dose) 10 days
Azithromycin 12 mg/kg PO once (max = 500 mg), then 6 mg/kg PO daily (max=250 mg)
5 days
Clarithromycin 7.5 mg/kg/dose PO bid (max = 250 mg/dose) 10 daysShulman ST, et al. Clin Infect Dis. 2012;55(10):e86-102.
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BRONCHITIS
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ETIOLOGY
Viral
¡ Influenza
¡ Parainfluenza
¡ Coronavirus types 1 to 3
¡ Rhinoviruses
¡ Respiratory syncytial virus
¡ Human metapneumovirus
Bacterial (<6% of cases)
¡ Mycoplasma pneumoniae
¡ Bordetella pertussis
¡ Chlamydophila pneumoniae
Harris AM , et al. Ann Intern M ed. 2016;164(6):425-34.
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COMMUNITY-ACQUIRED PNEUMONIA
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EPIDEMIOLOGY
¡ Most common cause of severe sepsis and infectious cause of death
¡ Eighth most common cause of death in the US
¡ 60,000 deaths in 2005
¡ 20-40% mortality rate (depending on severity)
¡ Incidence rate of 5.16 to 6.11 cases per 1000 persons per year
¡ Higher in men vs women
¡ Seasonal variation
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ETIOLOGY
¡ In most cases, no pathogens are detected¡ Viral pathogens cause ~1/4 of cases
¡ Human rhinovirus¡ Influenza A or B
¡ Bacterial pathogens cause ~1/7 of cases¡ Streptococcus pneumoniae¡ Staphyloccocus aureus¡ Haemophilus influenzae¡ Atypicals
¡ Mycoplasma pneumoniae
¡ Legionella pneumophila
¡ Chlamydophila pneumoniae
Jain S, et al. N Engl J Med. 2015;373:415-427.
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Jain S, et al. N Engl J Med. 2015;373:415-427.
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CURB-65
¡ Confusion – disorientation to person, place, or time
¡ Uremia – BUN ≥ 20 mg/dL
¡ Respiratory rate – tachypnea ≥ 30 breaths/min
¡ Blood pressure – SBP < 90 mmHg or DBP ≤ 60 mmHg
¡ Age ≥ 65 years
¡ Score can be used to determine setting of treatment
¡ ≤1 – Outpatient treatment
¡ 2 – Inpatient vs observation
¡ ≥ 3 – Admission (possibly to ICU)
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OUTPATIENT TREATMENT – TYPICALLY 5 DAYS
Previously healthy and no use of antimicrobials within the previous 3 months
¡ Macrolide¡ Azithromycin 500 mg PO x1, then 250 mg PO daily¡ Clarithromycin 500 mg PO BID or 1000 mg ER
daily¡ Consider alternative if >25% of Streptococcus
pneumoniae is macrolide-resistant
¡ Doxycycline 100 mg PO BID
¡ Amoxicillin 1000 mg PO TID
Presence of comorbidities or antimicrobial use within the previous 3 months
¡ Respiratory fluoroquinolone¡ Levofloxacin 750 mg PO daily¡ Moxifloxacin 400 mg PO daily
¡ β-lactam plus a macrolide (or doxycycline)¡ Amoxicillin 1000 mg PO TID¡ Amoxicillin/clavulanate 875/125 or 2000/125 mg PO
BID
¡ Cefpodoxime 200 mg PO BID¡ Cefuroxime 500 mg PO BID
Metlay JP, et al. Am J Respir Crit Care Med. 2019;200(7):e45-e67.
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NEW ANTIBIOTICS FOR CAP
Lefamulin (Xenleta)
¡ Pleuromutilin – protein synthesis inhibitor
¡ 600 mg PO q12h
¡ Non-inferior to moxifloxacin in LEAP 2
¡ Has not been studied in moderate or severe hepatic impairment
¡ Potentially lower risk of Clostridoides difficile
Omadacycline (Nuzyra)
¡ Aminomethylcycline – protein synthesis inhibitor
¡ 300 mg PO q24h on an empty stomach
¡ Non-inferior to moxifloxacin
¡ No renal or hepatic adjustments
¡ Low risk of Clostridoides difficile
Alexander E, et al. JAMA. 2019;322(17):1661-1671.Stets R, et al. N Engl J Med. 2019;380(6):517-527.
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INFLUENZA
Treatment
¡ Influenza A or B¡ Neuraminidase inhibitors preferably started within
48 hours of start of symptoms¡ Oseltamivir 75 mg PO BID x 5 days
¡ Zanamivir 10 mg (2 inhalations) BID x 5 days
¡ Peramivir 600 mg IV x 1 dose
¡ Cap-dependent endonuclease inhibitor¡ Baloxavir marboxil 40 mg (40-79 kg) or 80 mg (≥80 kg)
x 1 dose
Prophylaxis
¡ Influenza A or B¡ Neuraminidase inhibitors if initiated within 48 hours
of start of symptoms¡ Oseltamivir 75 mg PO daily x 7 days after exposure
¡ Zanamivir 10 mg (2 inhalations) daily x 7 days after exposure
Metlay JP, et al. Am J Respir Crit Care Med. 2019;200(7):e45-e67.Uyeki TM, et al. Clin Infect Dis 2018;68:e1–e47
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PREVENTION
¡ Modifiable risk factors
¡ Tobacco smoking
¡ Alcohol use disorder - treatment
¡ Acid-suppressant use
¡ Antipsychotic medications
¡ Immunization
¡ Influenza vaccination annually for everyone!
¡ Age ≥ 65 years
¡ Pneumovax (PPSV23)
¡ Prevnar (PCV13) is optional
¡ Age 2-64 years
¡ Pneumovax and/or Prevnar for high-risk groups
¡ Hib for high-risk groups
Mandell LA, et al. Clin Infect Dis. 2007;44(Suppl 2):S27–72
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CONCLUSION
¡ Antibiotics should generally start as narrow as possible and broadened in the case of resistance or non-response
¡ Treatment duration should be as short as possible
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QUESTIONS?
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